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  • 1
    ISSN: 1433-8580
    Keywords: Kidney ; Concentrating mechanism ; Corticomedullary gradients ; Urea ; Electrolytes ; Niere ; Konzentrierung ; Corticomedulläre Gradienten ; Harnstoff ; Elektrolyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung An wachen, eiweißarm ernährten Wistar-Ratten wurde die Wirkung von Harnstoff auf die renale Wasserretention und Elektrolytkonzentrierung unter standardisierten Bedingungen (Trinkwasserentzug, mehrtägige kombinierte hypertone Harnstoff/NaCl-Infusion) untersucht. Die Ergebnisse lassen erkennen, daß Harnstoff aktiv aus den Sammelrohren resorbiert wird und daß Natrium bei Harnstoffzufuhr stärker im Nierenmarkgewebe angereichert wird als bei reiner Elektrolytinfusion. Die bei Harnstoffzufuhr erhöhten medullären Konzentrationen bewirken einen zunehmenden osmotischen Wasserentzug aus den Sammelrohren ins Interstitium. Die Harnvolumina nehmen bei Anstieg der Elektrolytkonzentrationen entsprechend ab. Es wird geschlossen, daß die wasserretinierende Wirkung des Harnstoffs am besten nachgewiesen werden kann, wenn — bei kalkulierter Wasser- und osmotischer Substanzzufuhr — die GFR konstant gehalten wird, weiterhin das Nephron hoch permeabel für Harnstoff ist, also bei maximalen medullären Natriumkonzentrationen und Harnstoff über längere Zeit bei gleichbleibender Konzentration infundiert wird.
    Notes: Summary Subject of the examinations was the special effect of urea to the renal water retention and electrolyte concentrating ability on protein lacking rats under standardized conditions (no drinking, long-term combined hypertonic urea/saline infusions). The results show, that urea is reabsorbed actively out of the collecting ducts and that sodium is better enriched in the renal medulla during simultaneous urea supply than with pure electrolyte infusion. These increased medullary concentrations cause an enlarged osmotic water removal out of the collecting ducts into the interstitium during urea supply so that the urine volumes decrease and the electrolytes are better concentrated in the urine. It is concluded, that the water retaining effect of urea could be proved best when the glomerular filtrates are kept unchanged, furthermore when the nephron is high permeable for urea, that is by maximal medullary sodium concentration, and when urea is infused by longterm supply in constant rations.
    Type of Medium: Electronic Resource
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  • 2
    Publication Date: 2018-08-03
    Description: α v β 3 integrins play an important role in angiogenesis and cell migration in cancer and are highly expressed on the activated endothelial cells of newly formed blood vessels. Here, we compare the targeting characteristics of 4 68 Ga-labeled multimeric cyclic arginine-glycine-aspartate (RGD)–based tracers in an α v β 3 integrin–expressing tumor model and a tumor model in which α v β 3 integrin is expressed solely on the neovasculature. Methods: Female BALB/c nude mice were subcutaneously injected with SK-RC-52 (α v β 3 integrin–positive) or FaDu (α v β 3 integrin–negative) tumor cells. 68 Ga-labeled DOTA-(RGD) 2 , TRAP-(RGD) 3 , FSC-(RGD) 3 , or THP-(RGD) 3 was intravenously administered to the mice (0.5 nmol per mouse, 10–20 MBq), followed by small-animal PET/CT imaging and ex vivo biodistribution studies 1 h after injection. Nonspecific uptake of the tracers in both models was determined by coinjecting an excess of unlabeled DOTA-(RGD) 2 (50 nmol) along with the radiolabeled tracers. Results: Imaging and biodistribution data showed specific uptake in the tumors for each tracer in both models. Tumor uptake of 68 Ga-FSC-(RGD) 3 was significantly higher than that of 68 Ga-DOTA-(RGD) 2 , 68 Ga-TRAP-(RGD) 3 , or 68 Ga-THP-(RGD) 3 in the SK-RC-52 model but not in the FaDu model, in which 68 Ga-FSC-(RGD) 3 showed significantly higher tumor uptake than 68 Ga-TRAP-(RGD) 3 . Most importantly, differences were also observed in normal tissues and in tumor-to-blood ratios. Conclusion: All tracers showed sufficient targeting of α v β 3 integrin expression to allow for tumor detection. Although the highest tumor uptake was found for 68 Ga-FSC-(RGD) 3 and 68 Ga-THP-(RGD) 3 in the SK-RC-52 and FaDu models, respectively, selection of the optimal tracer for specific diagnostic applications also depends on tumor-to-blood ratio and uptake in normal tissues; these factors should therefore also be considered.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 3
    Publication Date: 2018-02-02
    Description: The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4-positive cell types in cardiovascular diseases such as atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of 68 Ga-pentixafor, a specific CXCR4 ligand for PET. Methods: The data for 51 patients who underwent 68 Ga-pentixafor PET/CT for noncardiovascular indications were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed qualitatively and semiquantitatively by blood-pool–corrected target-to-background ratios. Tracer uptake was compared with calcified plaque burden and cardiovascular risk factors. Results: Focal arterial uptake of 68 Ga-pentixafor was seen at 1,411 sites in 51 (100%) of patients. 68 Ga-pentixafor uptake was significantly associated with calcified plaque burden ( P 〈 0.0001) and cardiovascular risk factors including age ( P 〈 0.0001), arterial hypertension ( P 〈 0.0001), hypercholesterolemia ( P = 0.0005), history of smoking ( P = 0.01), and prior cardiovascular events ( P = 0.0004). Both the prevalence ( P 〈 0.0001) and the signal intensity ( P = 0.009) of 68 Ga-pentixafor uptake increased as the number of risk factors increased. Conclusion: 68 Ga-pentixafor PET/CT is suitable for noninvasive, highly specific PET imaging of CXCR4 expression in the atherosclerotic arterial wall. Arterial wall 68 Ga-pentixafor uptake is significantly associated with surrogate markers of atherosclerosis and is linked to the presence of cardiovascular risk factors. 68 Ga-pentixafor signal is higher in patients with a high-risk profile and may hold promise for identification of vulnerable plaque.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 4
    Publication Date: 2018-02-02
    Description: Because of its role in infection and inflammatory processes, the chemokine receptor CXCR4 might be a potent target in imaging of infectious and inflammatory diseases. The aim of this pilot study was to determine whether the CXCR4 ligand 68 Ga-pentixafor is suitable for imaging chronic infection of the bone. Methods: The study comprised 14 patients with suspected infection of the skeleton who underwent 68 Ga-pentixafor PET/CT between April 2015 and February 2017 in our facility. 68 Ga-pentixafor PET/CT results were retrospectively evaluated against a histologic, bacteriologic, and clinical standard. The results were also compared with available bone scintigraphy, white blood cell scintigraphy, and 18 F-FDG PET/CT results. Results: 68 Ga-pentixafor PET/CT was positive in 9 of 14 patients. Diagnoses included osteitis or osteomyelitis of peripheral bone, osteomyelitis of the maxilla, and infected endoprostheses. Target-to-background ratios were 5.1–15 (mean, 8.7). Eight of 9 cases were true-positive as confirmed by pathology, bacteriology, or clinical observation. All negative cases were confirmed as true-negative by other imaging modalities and follow-up. Conclusion: Imaging of CXCR4 expression with 68 Ga-pentixafor PET/CT appears suitable for diagnosing chronic infection of the skeleton. The findings of this study reveal a possible diagnostic gain in suspected chronic infections that are difficult to diagnose by other imaging modalities.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 5
    Publication Date: 2018-09-20
    Description: Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein–coupled receptors (GPCRs) called somatostatin receptor (SST)1–5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST 2 and SST 5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors. In addition, SST 2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and therapeutic interventions. This review article summarizes findings published in the last 25 years on the physiology, pharmacology, and clinical applications related to SSTs. We also discuss potential future developments and propose a new nomenclature.
    Print ISSN: 0031-6997
    Electronic ISSN: 1521-0081
    Topics: Chemistry and Pharmacology , Medicine
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  • 6
    Publication Date: 2018-03-06
    Description: Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading to esophageal adenocarcinoma. Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways in the development of Barrett's esophagus and esophageal adenocarcinoma. Experimental Design: Here we utilized an IL1β transgenic mouse model of Barrett's esophagus and esophageal adenocarcinoma and human patient imaging to analyze the importance of CXCR4-expressing cells during esophageal carcinogenesis. Results: IL1β overexpression induces chronic esophageal inflammation and recapitulates the progression to Barrett's esophagus and esophageal adenocarcinoma. CXCR4 expression is increased in both epithelial and immune cells during disease progression in pL2-IL1β mice and also elevated in esophageal adenocarcinoma patient biopsy samples. Specific recruitment of CXCR4-positive (CXCR4 + ) immune cells correlated with dysplasia progression, suggesting that this immune population may be a key contributor to esophageal carcinogenesis. Similarly, with progression to dysplasia, there were increased numbers of CXCR4 + columnar epithelial cells at the squamocolumnar junction (SCJ). These findings were supported by stronger CXCR4-related signal intensity in ex vivo fluorescence imaging and autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging studies in patients with esophageal cancer demonstrate the potential utility of CXCR4 imaging for the diagnosis and staging of esophageal cancer. Conclusion: In conclusion, the recruitment of CXCR4 + immune cells and expansion of CXCR4 + epithelial cells in esophageal dysplasia and cancer highlight the potential of CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor microenvironment in esophageal adenocarcinoma. Clin Cancer Res; 24(5); 1048–61. ©2017 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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